Follistatin: a multifunctional regulatory protein

Follistatin was first described in 1987 as a follicle-stimulating hormone inhibiting substance present in ovarian follicular fluid. We now know that this effect of Follistatin is only one of its many properties in a number of reproductive and nonreproductive systems. A majority of these functions are facilitated through the affinity of Follistatin for activin, where activin's effects are neutralized through its binding to Follistatin. As such, the interplay between Follistatin and activin represents a powerful regulatory mechanism that impinges on a variety of cellular processes within the body. In this review we focus on the biochemical characteristics of Follistatin and its interaction with activin and discuss the emerging role of these proteins as potent tissue regulators in the gonad, pituitary gland, pregnancy membranes, vasculature, and liver. Consideration is also given to the larger family of proteins that contain follistatin-like modules, in particular with regard to their functional and structural implications.